methimazole
Tapazole

Pharmacologic classification: thyroid hormone antagonist
Therapeutic classification: antihyperthyroid drug
Pregnancy risk category D


Available forms
Available by prescription only
Tablets: 5 mg, 10 mg

Indications and dosages
 Hyperthyroidism, preparation for thyroidectomy, thyrotoxic crisis. Adults: 15 mg P.O. daily if mild; 30 to 40 mg P.O. daily if moderately severe; 60 mg P.O. daily if severe. All are given in three equally divided doses q 8 hours. Continue until patient is euthyroid; then start maintenance dosage of 5 to 15 mg daily in divided doses. Maximum daily dose is 30 mg.
Children: 0.4 mg/kg daily P.O. divided q 8 hours. Continue until patient is euthyroid; then start maintenance dosage of 0.2 mg/kg daily divided q 8 hours.

Pharmacodynamics
Antihyperthyroid action: In treating hyperthyroidism, methimazole inhibits synthesis of thyroid hormone by interfering with the incorporation of iodide into tyrosyl. Methimazole also inhibits the formation of iodothyronine. As preparation for thyroidectomy, methimazole inhibits synthesis of the thyroid hormone and causes a euthyroid state, reducing surgical problems during thyroidectomy; as a result, the mortality for a single-stage thyroidectomy is low. Iodide reduces the vascularity of the gland, making it less friable. For treating thyrotoxic crisis (thyrotoxicosis), propylthiouracil theoretically is preferred over methimazole because it inhibits peripheral deiodination of thyroxine to triiodothyronine.

Pharmacokinetics
Absorption: Absorbed rapidly from the GI tract (80% to 95% bioavailable).
Distribution: Readily crosses the placental barrier and is distributed into breast milk. Drug is concentrated in the thyroid and isn’t protein-bound.
Metabolism: Undergoes hepatic metabolism.
Excretion: About 80% of drug and its metabolites are excreted renally; 7% is excreted unchanged. Half-life is between 5 and 13 hours.

Route Onset Peak Duration
P.O. Rapid 1/2-1 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in breast-feeding women. Use cautiously in pregnant women.

Interactions
Drug-drug. Adrenocorticoids, corticotropin, propylthiouracil: May require a dosage adjustment of the steroid when thyroid status changes. Monitor patient carefully.
Amiodarone, iodinated glycerol, lithium, potassium iodide: May potentiate hypothyroid and goitrogenic effects. Use together cautiously.
Anticoagulants: Anti-vitamin K action of methimazole potentiates the action of anticoagulants. Monitor PT and INR.
Beta blockers: May affect clearance of beta blockers. Monitor patient closely.
Bone marrow depressants: Increases risk of agranulocytosis. Monitor CBC.
Digoxin: Increases serum digoxin levels. Monitor levels closely.
Hepatotoxic drugs: Increases risk of hepatotoxicity. Monitor liver function tests. Use together cautiously.

Adverse reactions
CNS: headache, drowsiness, vertigo, paresthesia, neuritis, neuropathies, CNS stimulation, depression, fever.
GI: diarrhea, nausea, vomiting (may be dose-related), salivary gland enlargement, loss of taste, epigastric distress.
GU: nephritis.
Hematologic: agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia.
Hepatic: jaundice, hepatic dysfunction, hepatitis.
Metabolic: hypothyroidism.
Musculoskeletal: arthralgia, myalgia.
Skin: rash, urticaria, discoloration, pruritus, erythema nodosum, exfoliative dermatitis, lupus-like syndrome.
Other: lymphadenopathy.

Effects on lab test results
• May decrease hemoglobin and granulocyte, WBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, epigastric distress, fever, headache, arthralgia, pruritus, edema, and pancytopenia.
 Treatment is supportive; perform gastric lavage or induce emesis, if possible. If bone marrow depression develops, fresh whole blood, corticosteroids, and anti-infectives may be required.

Special considerations
• Best response occurs if dosage is administered around-the-clock and given at the same time each day with respect to meals.
• Doses of more than 40 mg daily increase the risk of agranulocytosis.
• A beta blocker, most often propranolol, is given to manage the peripheral signs of hyperthyroidism, primarily tachycardia.
• Euthyroid state may take several months to develop.
• Sulfonamide-type adverse reactions can occur.
• Monitor CBC in patients with signs and symptoms of illness.
• Monitor liver function test values, especially if hepatic dysfunction is suspected.
• Periodically monitor thyroid function tests.
Pregnant patients
• Drug can induce goiter and hypothyroidism in developing fetus. Manufacturer states that drug may be used judiciously to treat hyperthyroidism during pregnancy.
Breast-feeding patients
• Drug appears in breast milk. Patient should discontinue breast-feeding before beginning therapy. However, if breast-feeding is necessary, propylthiouracil is the preferred antithyroid drug.

Patient education
• Tell patient to take drug at regular intervals around-the-clock and to take it at the same time each day in relation to meals.
• If GI upset occurs, advise patient to take drug with meals.
• Tell patient to promptly report fever, sore throat, malaise, unusual bleeding, yellowing of eyes, nausea, or vomiting.
• Advise patient not to store drug in bathroom; heat and humidity cause it to deteriorate.
• Tell patient to inform other health care providers of drug use.
• Teach patient how to recognize the signs of hyperthyroidism and hypothyroidism and what to do if they occur.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use